Gallium is known to accumulate in certain tumors, inflamed tissue, and bone tissue by mechanisms that are largely unknown. Binding of gallium to transferring, particularly lactoferrin, is thought to be responsible for some of the transport of gallium in the body, and for the concentration of gallium in certain tumors and inflamed tissues. Radioactive 67gallium citrate compositions are used in patients to diagnose certain malignancies and infections, including those in bone tissue. Non-radioactive gallium compositions, and compositions containing other Group IIIa elements, have been found effective in treating some tumors in animals and humans. Gallium is thought to be the least toxic and most effective of these Group IIIa elements (Hart and Adamson, 1971). U.S. Pat. No. 4,596,710 discloses an anticancer treatment that uses gallium chloride. The gallium ion itself appears to be the active agent; the form in which the gallium is administered (e.g. as the nitrate, sulfate, or chloride) does not appear to affect its activity (Adamson et al., 1975).
Gallium appears particularly promising for treating and preventing hypercalcemia and certain bone diseases. Treatable bone diseases include such widespread conditions as osteoporosis, osteopenia, Paget's disease, malignant bone disease, and other conditions associated with increased bone resorption in humans or animals. U.S. Pat. Nos. 4,529,593 and 4,704,277 disclose treatments using gallium salts, preferably gallium nitrate, for regulating the resorption of calcium from bone in certain bone diseases and hypercalcemia, and for increasing the mass and tensile strength of bone.
If gallium is to be used as a treatment for widespread, chronic conditions such as osteoporosis (which affects over twenty million people in the United States), an oral form of gallium is needed that is safe and has high bioavailability. The currently preferred form of gallium (a composition containing mostly gallium nitrate) is absorbed from the gastrointestinal tract of dogs into blood serum in the amount of only 0.5-2% from an orally administered dose (U.S. Pat. No. 4,529,593). The percent absorption from other simple gallium salts is not likely to be significantly different, as such salts dissociate in aqueous solutions to produce mainly trivalent gallium ions, which appear to have very low absorbability from mammalian gastrointestinal tracts. The very low observed bioavailability may not be acceptable for an orally administered drug.
The compositions included in this invention were developed to provide sufficiently high gallium bioavailabilities, especially when administered orally, to be pharmaceutically acceptable for providing gallium to humans and animals.